Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage
Authors list
Tara E Sutherland Nicola Logan Dominik Rückerl Alison A Humbles Stuart M Allan Venizelos Papayannopoulos Brigitta Stockinger Rick M Maizels Judith E AllenAbstract
Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.
Journal details
Journal Nature Immunology
Volume 15
Issue number 12
Pages 1116-1125
Publication date
Full text links
Publisher website (DOI) 10.1038/ni.3023
Europe PubMed Central 25326751
Pubmed 25326751
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